Long-term exposure to Di(2-ethylhexyl) phthalate induced uterine histopathologic alterations in female mice

Objective: To investigate the effects of long-term Di(2-ethylhexyl) phthalate (DEHP) exposure on the female reproductive system, employing different dosages and durations of exposure. Methods: Pregnant female CD-1 mice (F0) were orally exposed to DEHP at doses of 0, 100, and 500 mg/kg/day during gestation. Following birth, the female offspring (F1) were allocated into three groups as F0 mice. Both F0 and F1 mice were consequently subjected to ongoing DEHP exposure until they were sacrificed. Body weight, anogenital distance, anogenital index (AGI), and histopathologic outcomes of the uterus were examined at 21 and 35 weeks for F0 mice and at 10 and 24 weeks for F1 mice. Results: Both low and high DEHP exposures significantly decreased body weight in F0 at 21 weeks and in F1 at 10 and 24 weeks, while AGI was not significantly changed in response to DEHP exposure in both F0 and F1 mice. DEHP exposure induced endometrial stromal fibrosis, endometrial hyperplasia, and myometrial atrophy in the uterus of F1mice, while cystic hyperplasia and endometrial stromal sarcoma (ESS) were seen in the F0 after DEHP exposure at 35 weeks. Conclusions: Long-term Exposure to DEHP significantly reduced body weight and induced pathological alterations in the uterus of both F0 and F1 mice. Dams exposed to high doses of DEHP developed ESS, suggesting that DEHP may have carcinogenic potential in the uterus. However, further research is necessary to confirm this finding.